Method and apparatus for determining variation over time of a medical parameter of a human being

ABSTRACT

An apparatus for determining variation over time of a medical parameter of a human being obtained from a sensed signal has a sensor implantable in the human being for sensing the signal. A comparator compares at least one characteristic property, derived from the sensed signal obtained for at least one predetermined first level of activity of the human being, with corresponding reference property of a sensed reference signal, obtained for a predetermined reference level of activity of the human being, for determining a relation between the characteristic property of the sensed signal and the reference property. A trend determining unit determines trends in the medical parameter by analyzing the relation between the characteristic property of the sensed signal obtained at different times and the reference property. A corresponding method also function an implant for heart failure diagnostics also function as described. A sensor is then arranged to pick up dynamic mechanical information from the heart of the human being and generate a corresponding signal. A heart stimulator includes such an implant and a control unit arranged to control stimulation of the heart depending on determined trends in the medical parameter.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to an apparatus and a method fordetermining variation over time of a medical parameter of a human being.The invention also relates to an implant for heart failure diagnosticscomprising such an apparatus as well as a heart stimulator includingsuch an implant to be used for controlling the stimulation.

2. Description of the Prior Art

The progress of medical parameters over time needs to be closelymonitored to minimize patient pain, discomfort and hospitalization.Thus, as an example, for this purpose the progress of the cardiacfunction must be closely monitored over time as the cardiac failurecondition changes.

An example of long term monitoring of a medical parameter is disclosedin U.S. Pat. No. 5,792,197. An implantable rate responsive pacemakeruses a physiological demand parameter to classify the patient's degreeof congestive heart failure. The parameter is monitored for extendedtime periods to determine the levels for this parameter for differentlevels of physical activity of the patient.

Implantable sensors are most often incapable of sensing staticinformation. The signal can be described as being dynamic. Due to this,it is of particular interest to be able to retrieve information for longterm monitoring from dynamic sensor signals obtained from implantedsensors.

SUMMARY OF THE INVENTION

An object of the present invention is to provide a technique fordetermining variations over time—trending—of a medical, diagnosticparameter obtained from the sensed dynamic signal of an implantedsensor.

The above object is achieved in accordance with the present invention byan apparatus for determining variation over time of a medical parameterof a human being obtained from a sensed signal, having a sensor that isimplantable in the human being for sensing the aforementioned signal. Acontroller operates the sensor to obtain a sensed referenced signal fora predetermined reference level of activity of the human being. Thecontroller also operates the sensor to obtain the sensed signal at anumber of different times for at least one predetermined level ofactivity of the human being. A comparator is supplied with the sensedsignal and the sensed reference signal, and determines a relationbetween a characteristic property, derived from the sensed signal, andthe same property derived from the reference sensed signal. A trenddetermining unit is supplied with this relation, and determinestherefrom a trend in a medical parameter of the human being by analyzingthe aforementioned relation.

Since some implanted dynamic sensors do not pick up any absolute signalmagnitudes, i.e. no DC signal, but only variations in the signal, i.e.AC signals, some sort of pseudo-zero-level or pseudo-reference must becreated for the comparisons from time to time needed for the trendanalysis as specified in the above mentioned claims. The relationsdetermined between characteristic properties of the sensor signal at thefirst level of activity and the reference level of activity of thepatient can be stored and displayed at follow-up or distributedcontinuously to a central diagnostic unit of a hospital for evaluation.

According to advantageous embodiments of the invention the implantablesensor is a piezoelectric pressure sensor. In his sensor, which isprimarily intended for cardiac use, the indifferent electrode lead iscoated by piezoelectric material, such that the output signal of thesensor contains both electric and pressure information. The dynamicpressure information includes several components and information ofinterest can be retrieved by suitable filtering.

The reference signal is sensed for a predetermined reference level ofactivity of the patient in question. The term activity in this contextincludes both actual physical activity of the patient and his or herbody position or posture. In principle any well-defined level ofactivity of the patient can be used as reference level of activity, e.g.the human being lying down resting or being at maximum activity.However, according to an advantageous embodiment of the apparatusaccording to the invention the predetermined reference level of activityof the patient is a situation of minimum activity. It is particularlysuitable to use the signal sensed during night-time when the patient isat sleep as reference signal, because posture changes during night-timedo not cause problems as the reference signal can be averaged over sometime with the patient at sleep. In its simplest form this can berealized by a clock-triggered analysis, for instance between 00.00 and02.00 am. In a more advanced solution combined informations from aclock, activity and posture sensors can be used for reference signaldetermination.

According to still another advantageous embodiment of the apparatusaccording to the invention the comparing means is arranged to determinerelations between the characteristic property of the sensed signal andthe reference property for more than one different level of activity ofthe human being, and the trend determining means is arranged todetermine trends in the medical parameter by analysing the relationsobtained for more than one different level of activity. In this way thequality of the trending analysis is improved.

According to yet another advantageous embodiment of the apparatusaccording to the invention an averaging means is provided to form anaverage reference signal measured during a certain time period for thereference level of activity of the human being for determining thereference property from the average reference signal. The referencesignal can be averaged over long time periods, e.g. months or evenyears. In this way the influence from temporary disturbances in thereference signal is reduced.

According to another advantageous embodiment of the apparatus accordingto the invention activity and posture sensors are provided to determinethe levels of activity of the patient. As mentioned above the term“activity” includes in this context both true physical activity of thepatient as well as his or her posture.

According to still another advantageous embodiment of the apparatusaccording to the invention calculating means is provided to form theroot-mean-square of the sensed signal, viz. the effect in the signal, asthe characteristic property.

According to yet another advantageous embodiment of the apparatusaccording to the invention a frequency analyzer is provided to determinethe fundamental and/or harmonics frequencies of the sensed signal ascharacteristic properties. Frequencies of the fundamental tone and oneor more harmonics are then determined, and/or the amplitudes of thesetones or harmonics. Also the quotient between e.g. frequencies of thefundamental tone and the first harmonics or the quotient betweencorresponding amplitudes can be used as characteristic property of thesignal.

According to other advantageous embodiments of the apparatus accordingto the invention a loop generator is connected to two units arranged todetermine two different quantities of the sensed signal for plottingrelated values of the quantities against each other to form a loop foreach signal period, and a comparator is connected to the loop generatorfor comparing the loop with a loop template calculated from thereference signal. One of these quantities can be the signal itself,received from the sensor, and the other one the time derivative of thesensed signal formed by a differentiating means. As characteristicproperty of the signal can then be chosen e.g. area within the loop,number of turn-arounds in the loop per signal period, the length of theradius to a point on the loop contour corresponding to a specific pointin the signal time period, or the angle which this radius forms to anaxis of a loop coordinate system.

According to still another advantageous embodiment of the apparatusaccording to the invention an alerting unit is arranged to be triggeredin response to a change in the reference property exceeding apredetermined limit within a predetermine time. Thus if a sufficientlylarge change is detected in the reference property from e.g. one datacollection point to another, this is reported for checking orevaluation, especially if this phenomenon is repeated the patient shouldbe called in for a check.

The invention also relates to an implant for heart failure diagnosticscomprising an apparatus as discussed above in which the sensor isarranged to pick up dynamic mechanical information from the heart of thepatient and generate a corresponding signal, as well as a heartstimulator embodying such an implant and a control means to controlstimulation of the heart depending on the determined trends in themedical parameter. Thus by implanting e.g. a piezoelectric sensor oranother pressure sensor in the heart of a patient these sensors willpick up dynamic mechanical information which can be used for heartfailure diagnostics and heart stimulation control to obtain e.g. truemechanical synchronization, AV- and VV-interval optimization in theoperation of the heart.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an example of a typical qualitative variation of aphysiologic parameter of a human being.

FIG. 2 shows a corresponding sensed signal for the variation shown inFIG. 1.

FIG. 3 is a flowchart schematically illustrating an embodiment of theinvention.

FIGS. 4-6 respectively show examples of the analysis of sensed signalsaccording to different embodiments of the invention.

FIG. 7 is a block diagram of an embodiment of the invention implementedin a pacemaker or an implantable cardio-defibrillator.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Dynamic sensing is of particular interest in the field of medicalimplants, since the sensor most often needs to be designed according tocoarse demands inside the body, thus disabling measurements of staticparameters. FIG. 1 shows qualitatively the typical variation of aphysiologic parameter as a function of time. As can be seen from FIG. 1the parameter is varying around a certain DC level. A correspondingsensed signal is not available. P-P denotes peak-to-peak.

FIG. 2 shows a corresponding sensed dynamic signal. As appears thevariation as a function of time is the same as in FIG. 1, but the usedsensor does not pick up the DC component but only the AC component, i.e.the variation information. The sensed signal in FIG. 2 is consequentlyvarying around the zero line of the diagram.

Trending analysis requires, however, some sort of zero or referencelevel for the necessary comparison analysis. A pseudo-zero or referencelevel must therefore be determined.

According to the present invention this pseudo-reference level isobtained from a signal sensed by the implanted sensor for apredetermined situation of the patient. This predetermined situation ofthe patient includes both a predetermined physical activity and apredetermined body position or posture of the patient. In the followingthe term “activity” of the patient will include the patient's physicalactivity as well as his or her posture.

For the determination of the reference level in principal anypredetermined activity of the patient, e.g. a minimum or a maximumactivity, can be used. In the following preferred embodiment thereference level will be determined for a minimum activity of thepatient. The reference level is thus preferably determined in nighttime, when the patient is asleep. The reference level is then preferablyobtained from a sensed reference signal which is averaged over some timewith the patient asleep. In this way possible influences from posturechanges of the patient in sleep state are minimized.

The easiest way of getting a reference level from an averaged sensedsignal is to use a clock-triggered function for this purpose, e.g. forusing an averaged sensor signal recorded between 00.00 and 02.00 a.m.The reference level can, however, be determined by a more advancedanalysis, for instance by using information from a clock, activity andposture sensors.

A mean value of reference levels obtained from this averaged detectorsignal during a plurality of nights, e.g. for total time periods ofmonths or even years, can also be formed. In this way the referencelevel, which is needed for the relation analysis, will not be lost in asituation of rapidly worsening conditions of the patient.

FIG. 3 is a flow-chart illustrating an example of the procedure in thepresent invention.

In block 2 the reference level is determined from the sensed signal at aminimum activity (rest or sleep), or another predetermined referenceactivity, of the patient 4.

In block 6 the signal is sensed by the implanted sensor atevery-day-activities or predefined activities of the patient. The sensedsignal is stored and/or processed at different times during the day. Thesignal can be acquired from the sensor continuously or on-demand,controlled by the patient 4, physician, or automatically by a device. Inthe on-demand mode the implant can be awakened by e.g. a communicationdevice.

Patient hand-held communication devices for patient-interactive therapywith an implanted device is previously known, cf. e.g. the systemHeartPod, marketed by the company Savacor, for measuring left atrialpressure interactively with the patient. This system also alerts thepatient when it is time to measure. A similar system can be used inconnection with the present invention too.

An activity sensor can be provided to sense the patient's activity andfor a predetermined activity automatically trigger storage or processingof the sensed signal. Alternatively, the predetermined activity can bydefined for instance by 5 steps in a staircase for the patient, or thelike.

In block 8 characteristic properties derived from sensed signals arecompared with corresponding reference properties of sensed referencesignals for determining a relation between the characteristic propertiesof the sensed signals and the reference properties. These relations canbe established for presently sensed signals as well as for previouslystored signals.

In block 10, finally, trends are determined in a medical parameterrelated to the sensed signal by analysing the above-mentioned relationsbetween the characteristic properties of the sensed signal andcorresponding reference properties over time. The trend is presented toa physician at e.g. follow-up or is transferred to a remote database fordiagnostic purposes.

The horizontal axis of the schematically shown coordinate system inblock 10 can represent time, and the vertical axis the magnitude ofquantity suitable for representing the trend. The arrows in block 10indicate examples of determined trends.

The characteristic properties of the sensed signals for the subsequentcomparison can be derived in different ways.

The reference signal can be stored as a template to form the referenceproperty with which the sensed signal itself is compared.

-   -   The root-mean-square, viz. the effect of the signal, can be        calculated as the characteristic property.    -   Two different quantities of the sensed signal can be determined,        and a loop generator is provided to plot related quantity values        against each other to form a loop for each signal period. An        example of such a loop is shown in FIG. 4. In this example a        differentiating unit is provided to form the time derivative,        d(SS)/dt, of the sensed signal, SS, and the shown loop is formed        of related values of d(SS)/dt and SS. Characteristic properties        of the signal can then be determined from e.g. the area within        the loop, the length of the radius to a specific point A on the        loop contour corresponding to a specific time in the signal        period, the angle α of the radius to point A, the number of        turn-arounds in the loop—two turn-arounds are shown in FIG.        4—and the general morphology of the loop. This kind of signal        processing has been previously used for other purposes, see e.g.        WO 2002/043587.    -   The variability of the signal period can be used as        characteristic property.    -   The fundamental and/or the harmonic frequency components of the        sensed signal can be used as characteristic properties. Thus the        frequencies of the fundamental tone of the signal as well as of        its first harmonics can be determined, or the amplitudes, of        these tones.

Relation between characteristic properties of the sensed signal andcorresponding reference properties are stored and displayed at follow-upor distributed to a central diagnostic unit at a hospital forevaluation, as explained above. FIGS. 5 and 6 illustrate two examples ofthe comparison analysis over time of sensed signal and reference level.The vertical axis represent a quantity corresponding to the signallevel.

In FIG. 5 signals DS are sensed for one defined activity level of thepatient. The reference level, which is an average value of DS during acertain time period of substantially constant level of activity of thepatient, is denoted by PZDS, represented by the first bar to the left inthe figure. Signals situated within an acceptance interval around PZDSare considered as normal according to preset criteria. For a couple ofdays, Day 1, Day 2, etc. the sensed signal DS is within the acceptanceinterval. Then a sensed signal DS appears, the sectioned bar, whichsignificantly exceeds the upper limit of the acceptance interval. Thisevent is highlightened for subsequent observations. Thereafter sensedsignals follow which fall within the acceptance interval.

FIG. 6 illustrates an example of the comparison analysis in a situationwhere signals are sensed for two different predefined levels ofactivity, Activity level 1 and Activity level 2, of the patient. In thiscase the inter-relation levels (DS-X_(n+1))-(DS-X_(n)) is trended,DS-X_(n) denoting the signal at period X and activity level number n.Thus DS-A₁ denotes the signal for activity level 1 in period A, DS-A₂the signal for activity level 2 in period A, DS-B₁ the signal foractivity level 1 in period B, etc. In this example the situation isconsidered as “normal”, provided the criterion (DS-X₁)<(DS-X₂) isfulfilled. From the figure it appears that this criterion is satisfiedfor Period A and Period B but not for Period C which event isconsequently highlighted for evaluation.

FIG. 7 is a block diagram of an implantable pacemaker or ICD providedwith an apparatus according to the invention, located within the dashedline in the figure.

A number of different, implantable sensors can be used in the presentinvention, viz. an activity sensor 12, a posture sensor 14, an oxygensensor 16, an impedance sensor 18 and a pressure sensor 20. One or moreof the sensors are connected through a sensor interface 22 to a signalprocessing, calculating and analysing device 24. Signals or sensorvalues from the sensor 12, 14, 16, 18, 20 are supplied to the device 24for storing in a memory 26 for subsequent use or processed and suppliedto a calculation unit 28 for calculation of one or more characteristicproperties. The calculated characteristic properties can be supplied tothe analysis unit 30 for establishing a relation to a stored referenceproperty and comparing this relation with stored relations, obtainedfrom previous measurements for determining trends in a medical parameterrelated to the sensed signal. Alternatively, the calculatedcharacteristic properties can be stored in the memory 26 for latertrending analysis.

A clock 32 is connected to the device 24 for setting the time for e.g.reading, through the sensor interface 22, sensed values to the device 24for processing and analysis. The clock can also control the time for thetrending analysis based on stored data. In case of time averaging of thesensed signal the clock 32 controls the period for the averaging, andthe clock 32 also controls the transfer of trend data to the controlunit 34 for the pacemaker or ICD 36.

The control unit 34 controls the therapy, i.e. the cardiac stimulationdelivered by the pacemaker 36 via electrodes implanted in a patient'sheart 38 by exchange of therapy data between the control unit 34 and thepacemaker 36.

The arrow 40 indicates that the sensors are preferably connected to thepatient's heart 38 through the pacemaker electrode system

Detected cardiac event markers are transferred to the control unit 34and there is a feedback from the control unit 34 to the processing andanalyzing device 24.

A telemetry unit 42 is provided for reading out data from the trendinganalysis at follow-up or for transfer to a central diagnostic stationfor evaluation. Also therapy data and other information can becommunicated by this unit between the implant and external equipments.

Although modifications and changes may be suggested by those skilled inthe art, it is the intention of the inventors to embody within thepatent warranted heron all changes and modifications as reasonably andproperly come within the scope of their contribution to the art.

1. An apparatus for obtaining variation over time of a medical parameterof a human being, comprising: a sensor configured for in vivoimplantation in a human being to sense a periodic physiological signalin the human being; a controller configured to operate said sensor toobtain said sensed signal for at least one predetermined level ofactivity of the human being and to obtain a sensed reference signal fromthe sensor for a predetermined reference level of said activity; a firstquantity determining unit that determines a first quantity from each ofsaid sensed signal said sensed reference signal; a second quantitydetermining unit that determines a second quantity from each of saidsensed signal and said sensed reference signal; a loop generator thatplots related values of said first and second quantities for saidreference signal to generate a loop template from said reference signaland that plots related values of said first and second quantities forsaid sensed signal to generate a loop in each period of said signal in acoordinate system having an origin and a coordinate system axis;comparator circuitry that compares a loop characteristic of said loop ineach period of said signal and in said loop template to determine arelation between said sensed signal and said sensed reference signal foreach period, said loop characteristic being selected from the groupconsisting of an angle that a radius of the origin to a predeterminedpoint on the loop contour, corresponding to a predetermined time in theperiod of said sensed signal, forms with respect to said coordinatesystem axis in each of said loop and said loop template, and a number ofturn-arounds within each loop and said loop template during each periodof said sensed signal; and a trend determining unit configured todetermine a trend in a medical parameter of the human being by analyzingsaid relation obtained for said different periods.
 2. An apparatus asclaimed in claim 1 wherein said sensor is a pressure sensor.
 3. Anapparatus as claimed in claim 1 wherein said sensor is a piezoelectricsensor that senses mechanical activity of the human being.
 4. Anapparatus as claimed in claim 1 wherein said controller is configured tooperate said sensor to obtain said sensed reference signal at areference level of activity that is a state of minimum activity for thehuman being.
 5. An apparatus as claimed in claim 1 comprising a storageunit wherein said loops for said respectively different periods arestored.
 6. An apparatus as claimed in claim 1 wherein said comparatorcircuitry is configured to determine said relation for multiple,different levels of said activity, and wherein said trend determiningunit is configured to determine said trend in said medical parameter byanalyzing the respective relations for said multiple, different levelsof said activity.
 7. An apparatus as claimed in claim 1 comprising atleast one of a posture sensor and an activity level sensor connected tosaid controller, that provide respective additional sensor signals tosaid controller to identify said level of activity and said referencelevel of activity.
 8. An apparatus as claimed in claim 1 wherein saidfirst quantity determining unit uses the sensed signal itself for thesensed reference signal itself as said first quantity, and wherein saidsecond quantity determining unit generates a time derivative of thesensed signal or a time derivative of the sensed reference signal assaid second quantity.
 9. An apparatus as claimed in claim 1 comprisingan alerting unit that is triggered to emit a humanly perceptible signalupon said trend determining unit identifying a change of said relationexceeding a predetermined limit within a predetermined time.
 10. Amethod for obtaining variation over time of a medical parameter of ahuman being, comprising the steps of: with a sensor configured for invivo implantation in a human being, sensing a periodic physiologicalsignal in the human being; operating said sensor to obtain said sensedsignal for at least one predetermined level of activity of the humanbeing and to obtain a sensed reference signal from the sensor for apredetermined reference level of said activity; automaticallyelectronically determining a first quantity from each of said sensedsignal said sensed reference signal; automatically electronicallydetermining a second quantity from each of said sensed signal and saidsensed reference signal; in a loop generator, plotting related values ofsaid first and second quantities for said reference signal to generate aloop template from said reference signal and that plots related valuesof said first and second quantities for said sensed signal to generate aloop in each period of said signal in a coordinate system having anorigin and a coordinate system axis; in comparator circuitry, comparinga loop characteristic of said loop in each period of said signal and insaid loop template to determine a relation between said sensed signaland said sensed reference signal for each period, said loopcharacteristic being selected from the group consisting of an angle thata radius of the origin to a predetermined point on the loop contour,corresponding to a predetermined time in the period of said sensedsignal, forms with respect to said coordinate system axis in each ofsaid loop and said loop template, and a number of turn-arounds withineach loop and said loop template during each period of said sensedsignal; and automatically electronically determining a trend determiningunit configured to determine a trend in a medical parameter of the humanbeing by analyzing said relation obtained at said respectively differenttimes.
 11. A method as claimed in claim 10 comprising implanting apressure sensor as said sensor.
 12. A method as claimed in claim 10comprising implanting a piezoelectric sensor that senses mechanicalactivity of the human being as said sensor.
 13. A method as claimed inclaim 10 comprising operating said sensor to obtain said sensedreference signal at a reference level of activity that is a state ofminimum activity for the human being.
 14. A method as claimed in claim10 comprising electronically storing said loops for respectivelydifferent periods.
 15. A method as claimed in claim 10 comprisingdetermining said relation for multiple, different levels of saidactivity, and determining said trend in said medical parameter byanalyzing the respective relations for said multiple, different levelsof said activity.
 16. A method as claimed in claim 10 comprising, withat least one of a posture sensor and an activity level sensor providingrespective additional sensor signals that identify said level ofactivity and said reference level of activity.
 17. A method as claimedin claim 10 comprising using the sensed signal itself for the sensedreference signal itself as said first quantity, and generating a timederivative of the sensed signal or a time derivative of the sensedreference signal as said second quantity.
 18. A method as claimed inclaim 10 comprising triggering emission of a humanly perceptible signalupon identifying a change of said relation exceeding a predeterminedlimit within a predetermined time.
 19. A heart stimulator comprising: asensor configured for in vivo implantation in a human being to sense aperiodic physiological signal in the human being; a controllerconfigured to operate said sensor to obtain said sensed signal for atleast one predetermined level of activity of the human being and toobtain a sensed reference signal from the sensor for a predeterminedreference level of said activity; a first quantity determining unit thatdetermines a first quantity from each of said sensed signal said sensedreference signal; a second quantity determining unit that determines asecond quantity from each of said sensed signal and said sensedreference signal; a loop generator that plots related values of saidfirst and second quantities for said reference signal to generate a looptemplate from said reference signal and that plots related values ofsaid first and second quantities for said sensed signal to generate aloop in each period of said signal in a coordinate system having anorigin and a coordinate system axis; comparator circuitry that comparesa loop characteristic of said loop in each period of said signal and insaid loop template to determine a relation between said sensed signaland said sensed reference signal for each period, said loopcharacteristic being selected from the group consisting of an angle thata radius of the origin to a predetermined point on the loop contour,corresponding to a predetermined time in the period of said sensedsignal, forms with respect to said coordinate system axis in each ofsaid loop and said loop template, and a number of turn-arounds withineach loop and said loop template during each period of said sensedsignal; and a trend determining unit configured to determine a trend ina medical parameter of the human being by analyzing said relationobtained at said respectively different times; and stimulating circuitryconfigured for interaction with the heart of the human being tostimulate the heart dependent on said trend in said medical parameter.20. A heart stimulator as claimed in claim 19 wherein said heartstimulator comprises an intracorporeal communication unit configured totransmit signals representing said relation, determined for saiddifferent periods, to an extracorporeal receiver.